Intellectual disabilities (ID) represent a large and heterogeneous group of cognitive disorders. Robust genome interrogation methods applied to ID patients are revealing numerous genes that are crucial for cognitive functioning. However, knowledge about the normal and pathophysiological processes involving ID genes is still in its infancy. An emerging concept is that ID genes are hubs in a selected number of key signalling pathways whose dysregulation underlies synaptic and cortical network dysfunction. Moreover, evidence is accumulating that chromatin modifications are important in cognitive processes and in the etiology of an increasing number of ID disorders. Here we propose a strategy to study the genes identified in a clinical well-defined ID syndrome as an excellent stepping-stone to understand how the corresponding proteins contribute to synaptic function and ultimately to learning and memory. We will study a chromatin-modification module that underlies a recognizable form of ID. This module consists of EHMT1, MBD5, MLL3, SMARCB1, and NR1I3, all of which encode epigenetic regulators of transcription. Here we will test the hypothesis that a genetic hit in each of these genes will lead to a similar cellular outcome at the level of synaptic and network (dys)function. To this end we will use the potential of human-derived induced pluripotent stem cells (hIPSC) and differentiate them into neurons (iNeurons). Subsequently, we will measure neural network formation and maturation capabilities by functionally characterizing these iNeurons at the level of synaptic activity and network properties during development. Together our experiments will provide insight into the ?multiple gene-one outcome hypothesis?.